Method for determination of analyte concentrations and related apparatus

ABSTRACT

A method is provided for determining analyte concentrations, for example glucose concentrations, that utilizes a dynamic determination of the appropriate time for making a glucose measurement, for example when a current versus time curve substantially conforms to a Cottrell decay, or when the current is established in a plateau region. Dynamic determination of the time to take the measurement allows each strip to operate in the shortest appropriate time frame, thereby avoiding using an average measurement time that may be longer than necessary for some strips and too short for others.

BACKGROUND

This application relates to a method for detection of analyteconcentration using an electrochemical test strip, and to a meter andmeter test strip combination for use in such a method.

Small disposable electrochemical test strips are frequently used in themonitoring of blood glucose by diabetics. Such test strips can also beemployed in the detection of other physiological chemicals of interestand substances of abuse. In general, the test strip comprises at leasttwo electrodes and appropriate reagents for the test to be performed,and is manufactured as a single use, disposable element. The test stripis combined with a sample such as blood, saliva or urine before or afterinsertion in a reusable meter, which contains the mechanisms fordetecting and processing an electrochemical signal from the test stripinto an indication of the presence/absence or quantity of the analytedetermined by the test strip.

Electrochemical detection of glucose is conventionally achieved byapplying a potential to an electrochemical cell containing a sample tobe evaluated for the presence/amount of glucose, an enzyme that oxidizesglucose, such as glucose oxidase, and a redox mediator. As shown in FIG.1, the enzyme oxidizes glucose to form gluconolactone and a reduced formof the enzyme. Oxidized mediator reacts with the reduced enzyme toregenerate the active oxidase and produce a reduced mediator. Reducedmediator is oxidized at one of the electrodes, and then diffuses back toeither be reduced at the other electrode or by the reduced enzyme tocomplete the cycle, and to result in a measurable current. The measuredcurrent is related to the amount of glucose in the sample, and varioustechniques are known for determining glucose concentrations in such asystem. (See, U.S. Pat. Nos. 6,284,125; 5,942,102; 5,352,2,351; and5,243,516, which are incorporated herein by reference.)

Improvements in test strip design are driven by several considerations,including the need for accuracy and a desire for production of rapidresults. The time required for correct measurement to occur, however,can be variable as a result of sample characteristics and variability ofthe test device. Thus, devices which perform a measurement at a fixedtime after sample insertion have to make compromises in order tomaximize the likelihood of sufficient time having passed. Thiscompromise lengthens the time required to do a measurement, and maystill fail to deal with samples and test devices that fail to conform toanticipated averages. Since performance of duplicate tests requires alevel of user participation that may not be obtained, it would bedesirable to have a glucose test system that did not make thesecompromises.

SUMMARY OF THE INVENTION

The present application provides a method for determining analyteconcentrations, for example glucose concentrations, that utilizes adynamic determination of the appropriate time for making a glucosemeasurement, for example when a current versus time curve substantiallyconforms to a Cottrell decay, or when the current is established in aplateau region.

When determining analyte from a measurement of Cottrell current, thestarting time, t_(meas) for the measurement is established dynamicallyat a time after t_(peak) when the observed current profile substantiallyconforms to Cottrell decay. In specific embodiments, this time set is amultiple of the time of maximum observed current, t_(peak), where themultiple is determined for a given test strip configuration. In otherembodiments, the t_(meas) is t_(peak)+a constant, for example plus 1.5to 2.5 seconds. In the general case, t_(meas)=a₁×t_(peak)+a₂ with eitheror both of empirically determined constants being utilized. Makingglucose determinations based on the observed currents at these timesresults in determinations with improved reliability, and also minimizesthe time required for sample evaluation for any given sample. Thus, themethod of the invention provides superior performance and more robustresults.

When making measurements in the plateau region, the starting timet_(meas) is determined once the change in current with time has passedbelow a predetermined threshold value, or may be determined as eithert_(peak) plus a constant or t_(peak) times a constant. The numericalvalues of these constants in each case are determined empirically for agiven test strip and meter, since the optimum time will depend onfactors such as electrode spacing and chemistry, and the appliedvoltage.

The present invention also provides an apparatus with appropriateelectronic components for dynamic determination of the location oft_(peak), and for collection of current data at the desired timethereafter. The apparatus has a housing with a slot for introduction ofan electrochemical test strip, means for communicating/displaying adetermined analyte level to a user, and the necessary electronics toprocess the sample and convert measured values into acommunicated/displayed analyte level. The invention further provides acombination of such a meter with an electrochemical test strip.

The value of t_(peak) can also be used to check for errors in themeasurement which leads to an error indication from the meter. Forexample, if t_(peak) is outside of an empirically determined range, thenan error state should be established by the meter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the electron transfer reactions that occur in aconventional amperometric glucose detector.

FIG. 2 show the type of current versus time profiles observed in twodifferent electrochemical test strip configurations.

FIG. 3A-D show signal processing options for locating a preferredt_(meas) in a Cottrell analysis.

FIG. 4 shows projected run time in test strips which were intended foruse with a Cottrell current measurement occurring at 8 sec.

FIG. 5 shows the operation of the meter of the invention in schematicform.

FIG. 6 shows an exterior view of a meter.

FIG. 7 shows connection of a test strip and connectors in a meter.

DETAILED DESCRIPTION OF THE INVENTION I. Definitions

As used in the specification and claims of this application, thefollowing definitions should be applied:

(a) “analyte” refers to a material of interest that may be present in asample. In the present application, the examples use glucose as ananalyte, but the present invention is independent of both the type andamount of analyte. Accordingly, application to glucose detection systemsshould be viewed as merely a specific and non-limiting embodiment. Insome cases, there may be one or more intermediate species between theactual analyte and the mediator. Any such intermediate species are alsoreferred to herein as an analyte.

(b) “Cottrell decay” or “Cottrell current” is current that can bemodeled by the Cottrell equation, i.e.,1/l²∝t

where l is the current and t is time. The square root of the slope of1/l² versus t is a parameter called the “Cottrell slope.”

(c) “determination of an analyte” refers to qualitative,semi-quantitative and quantitative processes for evaluating a sample. Ina qualitative evaluation, a result indicates whether or not analyte wasdetected in the sample. In a semi-quantitative evaluation, the resultindicates whether or not analyte is present above some pre-definedthreshold. In a quantitative evaluation, the result is a numericalindication of the amount of analyte present.

(d) “electrochemical test strip” refers to a strip having at least twoelectrodes, and any necessary reagents for determination of an analytein a sample placed between the electrodes. In preferred embodiments, theelectrochemical test strip is disposable after a single use, and hasconnectors for attachment to a separate and reusable meter that containsthe electronics for applying potential, analyzing signals and displayinga result.

(e) “facing electrodes” are a pair of electrodes disposed parallel tobut in a separate plane from each other. Some or all of the opposedsurfaces of a pair of facing electrodes overlap, such that potentialgradients and current flows between the electrodes are in a directionsubstantially perpendicular to the opposed surfaces. Facing electrodesare distinguished from side-by-side electrodes in which the twoelectrode surfaces lie in the same plane, and in which potentialgradients and current flow is substantially parallel to the surface ofthe electrodes. The present invention can be used with either facing orside-by-side electrodes.

(f) “dynamic determination” refers to the determination of a valueduring the course of the measurement cycle for a particular sample. Forexample, dynamic determination of the time t_(peak) determines that timeat which maximum current occurs during the course of the measurementcycle of the sample being processed in the individual test strip,exclusive of any initial current spike associated with double-layercharging.

(g) “mediator” refers to a chemical species that is electrochemicallydetected. Numerous electron transfer mediators suitable for detection ofanalytes such as glucose are known, and include without limitation iron,ruthenium, and osmium compounds. In some embodiments of the invention,the mediator is produced through one or more reaction steps and isrelated to the concentration of the actual analyte, such as glucose. Thepresent invention is also applicable, however, to circumstances in whichthe detected chemical species is the reduced form of the analyte to bedetected, and this is also an embodiment of the invention.

(h) “t_(meas)” refers to the time at which a measurement of current ismade for purposes of obtaining data for determination of an analyte. Ina Cottrell measurement where the Cottrell slope is to be determined, atleast two data points at different times are required. In this case,t_(meas) refers to the start or center of the measurement window,whichever conditions are used in determining the empirical constants.Where a single data point is sufficient, for example when a plateaucurrent is measured, t_(meas) refers to the time at which this datapoint is taken.

(i) “t_(peak)” is the time at which maximum current occurs during thecourse of the measurement cycle of the sample being processed in theindividual test strip, exclusive of any initial current spike associatedwith double-layer charging. This peak current occurs at the point ofchangeover when sufficient material is available at the counterelectrode to balance the consumption of analyte or mediator at theworking electrode. At this point, the consumption of analyte or mediatorat the working electrode becomes limiting. This rapid fall in currentthat results from the diffusion-limited consumption of analyte is whatgives rise to the characteristic Cottrell decay.

II. Detection of Analyte, for Example Glucose

FIG. 2 shows current versus time profiles observed in two differentelectrochemical test strip configurations, one with facing electrodesand one with side-by-side electrodes, where the electrochemical reagentsare initially disposed only on the working electrode, and not on thecounter electrode. In both cases, the current trace shows an immediateinitial current 21 on the time scale shown following application of thepotential. This current is associated with the initial charging of thedouble layer at the surface of the electrodes. Thereafter, the currentdecreases, because current is dependent on the mediator diffusing fromthe working electrode (where the reagent comprising the mediator wasdeposited during manufacture) to the counter electrode. The duration ofthis reduced current (indicated by arrow 20) is dependent on thedistance between the electrodes, and on the mobility of the mediator.Mediator mobility is a property of the mediator itself, i.e., thediffusion coefficient, but is also dependent on other sample propertiessuch as hematocrit and viscosity. After the period of reduced current20, the current rapidly rises to a peak current 22. In the case offacing electrodes, the current declines to a plateau current 23 whichreflects the recycling or shuttling of mediator between the electrodes.In the case of side-by-side electrodes, the current continues to decayin the time scale indicated, as indicated by dashed line 24. At longertimes, this curve 24 may also shows effects of recycling/shuttling ofmediator if the electrodes are placed close enough together.

In the region of the decay following the peak, before recycling becomesdominant, the current decay can be modeled by the Cottrell equation,i.e.,1/l₂∝t

where l is the current and t is time. Cottrell analysis can be utilizedto determine glucose concentration as described in U.S. Pat. Nos.5,243,516; 5,352,351 and 6,284,125. Commonly assigned U.S. patentapplication Ser. No. 10/907,803, which is incorporated herein byreference, discloses a Cottrell analysis of analyte concentration thatincludes a mobility correction obtained when the applied potential isswitched off after monitoring the current to obtain data fordetermination of analyte.

As an alternative to Cottrell analysis, current in the plateau region 23of FIG. 2 can be used to determine analyte concentration. This type ofmeasurement is particularly applicable when using conduction cell teststrips, as described in commonly assigned U.S. patent application Ser.No. 10/924,510, which is incorporated herein by reference.

In determining the numerical value of analyte concentration which iscommunicated/displayed to a user, one or more correction factors basedon calibration values for a lot of strips, or measurements made duringthe analysis may be applied. Further, it will be understood that a lookup table or other conversion system may be used to convert a raw valueinto a meaningful value for communication/display to the user.

III. Determination of t_(peak)

The present invention uses a determination of t_(peak) as a basis for adynamic determination of the time, t_(meas), at which measurement willbe made or commenced.

In accordance with the invention, a sample in a electrochemical teststrip is processed to generate a current profile as shown in either linein FIG. 2. Thus, in a first step, a diffusion-limiting voltage isapplied to a test strip rapidly after a sample is introduced to thechamber. The polarity of the electrodes is such that a firstelectrochemically detectable species whose concentration depends on theanalyte will be consumed at the electrode the reagent is deposited onone electrode (the ‘working electrode’, and balanced by a counterreaction of a second species in excess in the reagent at the oppositeelectrode (the ‘counter electrode’). In this way, a signal limited byconsumption of the first species will not occur until there is excess ofthe second species at the opposite electrode, a condition that islimited by mobility. The voltage applied to the test strip to stimulatea current through the sample should be sufficiently high to ensure thecurrent reaches a limit set by the mobility of species, the so-called“diffusion limited current.” Further, this voltage needs to have beenapplied sufficiently early that the change from current limited byarrival of species at the counter electrode to current limited byarrival of analyte-dependant species (analyte or mediator) at theworking electrode can be observed under diffusion-limited conditions.

The initial current surge associated with application of the potential(due to establishing electrode double layers and consuming surfaceimpurities) must have had sufficient time to die away to leave abaseline current that represents arrival of species at the counterelectrode. This baseline is monitored and will start to increase rapidlywhen significant amounts of species become available to support reactionat the counter electrode. The rapid increase is monitored and a point ofchangeover noted. This changeover occurs when sufficient species areavailable to support reaction at the counter electrode to balanceconsumption of analyte-dependent species at the working electrode, whichthen becomes limiting. The time to this changeover is thus an indicatorof mobility, and is designated in this application as t_(peak). Thechange in limiting species results in the rapid consumption ofanalyte-dependent species near the working electrode and a rapid fall inthe current as a result.

Identification of the peak is done by inspecting amperometric data as itis produced for a local maximum. Such inspection is best not started tooearly since filling, patient contact with the sample and initial currentsurges should be ignored: starting inspection from a time point of 1 to2 seconds, for example 1.5 seconds after sample detection is adequatefor most sub microliter electrochemical test strips. In one embodimentfor the invention, the local maximum is the highest current in a timewindow from the present stretching back a set period: two seconds isgood because it fits well with the time that must elapse forestablishing a stable diffusion profile. When the local maximum is atthe earliest point of the time window and has not been replaced by ahigher maximum in later data, the peak can be assumed to have beenidentified as this local maximum. Identification can be improved furtherby applying digital or analogue filters to remove the effects of sharpspikes in the data that are not representative of diffusional processes.Other techniques, such as curve fitting to identify peaks of aparticular expected form may also be used, or the amperometric signalcan be evaluated to determine the time when the first derivative iszero.

In order to obtain a value for t_(peak) which is an accurate measure ofthe time from the introduction of the sample, a mechanism for definingthe start of the measurement cycle is required. As is apparent fromlooking at FIG. 2, the numerical value of t_(peak) is dependent on thepoint in time which is assigned a zero value. If blood is applied to atest strip and a period of time is allowed to pass prior to starting thetest cycle, enzyme and mediator will dissolve and tend to diffuse acrossevenly in the space between the electrodes. This will result in theshortening, if not the elimination of the interval 20. Thus, inpracticing the method of the invention, it is important to have aconsistent start time relative to sample application that is beforediffusion to eliminate interval 20 can occur. In practice, this resultcan be obtained by automatically starting the cycle upon, or within afixed period of time after the addition of sample to an electrochemicaltest strip that is already disposed in the meter.

Mechanisms for automatically starting the measurement cycle include,without limitation,

(1) measuring a current or a resistance between the working and counterelectrodes in the electrochemical test strip; and

(2) measuring a current or a resistance between two electrodes whereinat least one of the two electrodes is not the working electrode or thecounter electrode. Thus, the current or resistance could be measuredbetween a combination of a third electrode and either the working orcounter electrode, or between a third and fourth electrode. It will beappreciated that the current measured in this case can be a current inresponse to a low voltage, insufficient to produce redox chemistryindicative of analyte, although this requires a sample that has ioniccharge carriers such as Na+ and Cl— either inherently present or added.

Sample detection to initiate timing of an assay may also be donepassively as described in US Patent Publication US2003/0106809, which isincorporated herein by reference.

In one embodiment of the invention, while the meter is waiting forsample to be introduced after having been turned on by the user or bydetection of a sample strip, it is pulsing the voltage, Vw, of theworking electrode while holding the voltage, Vc, of the counterelectrode constant. This pulsed voltage can conveniently be shapedalmost as a sine wave using a low pass filter on Vw. The frequency ofpulsing is dependent on the hardware chosen, and is suitably in therange of 20 to 50 Hz, for example 33 or 40 Hz.

When sample is introduced, the current traveling through the electrodesshould spike with each pulse. To make a more reliable determination thatsample has been introduced, however, in one embodiment of the invention,a plurality of consecutive spikes are required to count as an indicationof sample application. For example, a positive indication of sampleapplication may require a current spike in response to 3 of 4, 4 of 5, 4of 6, or 6 of 8 consecutive voltage pulses.

Calculation of the starting time is based on an assumed sampleapplication time prior to the triggering time. For example, in the casethat 3 of 4 current spikes are required, it is assumed that sample wasintroduced 3 voltage pulses before the trigger. Therefore, the triggerhappens at: t=(3/pulse frequency). In the case that 6 of 8 currentspikes are required, it is assumed that sample was introduced 6 voltagepulses before the trigger. Therefore, the trigger happens at: t=(6/pulsefrequency). The times t_(peak) and t_(meas) are determined withreference to this zero time.

While the Cottrell equation effectively models the decay of the currentfor a portion of the decay time following the peak current, the locationof the peak is both sample and test strip dependent, and because thetotal duration of decay is short, it is difficult to staticallydetermine a time that ensures measurements in this time zone in apractical working device. The same is true of plateau currents. Thepresent application provides an improved method for determining when toperform the Cottrell or plateau analysis using a dynamic determinationof t_(peak). Accordingly, the present method allows each strip tooperate in the shortest appropriate time frame, thereby avoiding usingan average measurement time that may be longer than necessary for somestrips and too short for others. (See FIG. 4 and Example 1 below).

IV. Determination of t_(meas) for a Cottrell Analysis

Once t_(peak) t is determined, this value may used to dynamicallydetermine the time t_(meas) at which the Cottrell decay should besampled to assess glucose concentration. In a general sense, it isdesirable to make the measurement at a time after t_(peak) when thechange in current over time most closely conforms to an ideal Cottrelldecay. This can be accomplished in several ways, using either ananalysis of collected current data in the time period following t_(peak)or by setting t_(meas) to be equal to t_(peak) plus a predeterminednumber of seconds or times a predetermined factor, or a combination ofboth.

t_(meas) can be established by analysis of collected data points in thetime period following t_(peak) t to determine a time when the signalconforms to Cottrell decay. FIG. 3A-D outlines various signal processingoptions for accomplishing this result. FIG. 3A shows the unprocessedcurrent as a function of time with the Cottrell region indicated. In oneembodiment, the method involves processing the signal and identifying alocal minimum in the first derivative. (FIG. 3B). In another embodiment,the second derivative of the current as a function of time (FIG. 3C) isevaluated and t_(meas) is selected as the time at which the signal issubstantially zero, for example −0.1 to 0.1. In yet another embodiment,the signal is processed to identify a maximum in d(1/l²)/dt (FIG. 3D).

As a practical alternative to processing the signal in this manner, ithas been found that for a given specific electrochemical test strip,t_(meas) can be defined as a simple multiple of t_(peak) for example amultiple in the range of 1.2 to 1.4, for example between 1.25 and 1.35.The specific value of suitable and optimum multiple for a given teststrip design can be determined using the procedures described below inthe example. t_(meas) can also be determined dynamically by adding adefined period of time, for example 1.5 to 2.5 seconds, to t_(peak). Inthe general case, t_(meas)=a₁×t_(peak)+a₂ with either or both ofempirically determined constants being utilized.

These two techniques can also be used in combination. In thisembodiment, a test value of t_(test) equal to t_(peak) times apre-determined factor or t_(peak) plus a predetermined number of secondsis used as the starting point for analysis of the data points todetermine the best fit to the Cottrell decay. This minimizes the dataprocessing required, and thus accelerates the time to a result for theuser.

V. Determination of t_(meas) for a Plateau Analysis

Once t_(peak) is determined, this value may used to dynamicallydetermine the time t_(meas) at which a plateau current should be sampledto assess glucose concentration. In a general sense, it is desirable tomake the measurement at a time after t_(peak) when the change in currentover time is minimal. This can be accomplished in several ways, usingeither an analysis of collected current data in the time periodfollowing t_(peak) or by setting t_(meas) to be equal to t_(peak) plus apredetermined number of seconds or times a predetermined factor, or acombination of both.

Establishment of t_(meas) can be established by analysis of collecteddata points in the time period following t_(peak) to determine a timewhen the change in the signal is substantially zero, i.e, less than3%/sec. As a practical alternative to processing the signal in thismanner, it has been found that for a specific electrochemical teststrip, t_(meas) can be defined as a simple multiple of t_(peak) forexample a multiple in the range of 1.5 to 5, for example between 3.8 and4.7. The specific value of suitable and optimum multiple for a giventest strip design can be determined using the procedures described belowin the example. For plateau current measurements, t_(meas) can also bedetermined dynamically by adding a defined period of time, for example 6to 10 second to t_(peak).

These two techniques can also be used in combination. In thisembodiment, a test value of t_(test) equal to t_(peak) times apre-determined factor or t_(peak) plus a predetermined number of secondsis used as the starting point for analysis of the data points todetermine the point when threshold slope is achieved, if it has notalready done so. This minimizes the data processing required and thusaccelerates the time to a result for the user, yet ensures that aplateau current has been established.

VI. Error Detection Based on t_(peak)

In accordance with an additional embodiment of the invention, t_(peak)can be used independently or additionally as a basis for detectingmeasurement errors and returning an error rather than a result to theuser.

For any given test strip, t_(peak) should fall within a defined range ofvalues. Various errors can occur, however, which will cause t_(peak) tofall outside this range. For example, t_(peak) may be too small if

-   -   an inappropriate sample is used, for example a non-blood sample        since the number of red blood cells influences t_(peak)    -   some reagent flakes off of working electrodes and is therefore        closer to the counter electrode at the time of sample addition.

The observed value for t_(peak) may also be too high, for example if

-   -   a blood sample with too high a value for hct is used. For        example, neonates may have hct values of up to 70%.    -   manufacturing errors that give rise to an electrode spacing that        is too large.

The actual values that are appropriate for t_(peak) are strip-dependentand are therefore appropriately determined empirically by simulatingerrors of the type described above.

The method of the invention may include the step of comparing thedetermined value of t_(peak) to a predetermined range, and returning anerror message when the determined value falls outside of the range.Further, this evaluation can be used separately, even in meters wherethe time for taking the measurement is not dynamically determined.

VI. Apparatus of the Invention

The method of the invention can be used with any strip that has aworking and counter electrodes, and a diffusible mediator in one redoxstate (oxidized or reduced) that is initially deposited on or in thevicinity of only one electrode (the working electrode) wherein thepositioning of the electrodes and the mobility of the mediator are suchthat mediator will dissolve and diffuse from the working electrode tothe counter electrode during the time scale of the measurement, incombination with a meter apparatus that can receive the strip andprovide the necessary applications of voltage and signal processing.Such a meter also forms an aspect of the present invention. Thus, theinvention provides a meter for receiving an electrochemical test striphaving electrodes and providing a determination of an analyte in asample applied to the electrochemical test strip when received in themeter, said meter comprising

(a) a housing having a slot for receiving an electrochemical test strip;

(b) communications means for receiving input from and communicating aresult to a user; and

(c) means for determining t_(peak) and dynamically determining t_(meas)based upon the determined value of t_(peak).

FIG. 5 shows a schematic representation of the operation of a meter inaccordance with the invention. As shown in FIG. 5, potential 51 isgenerated by circuit 55 and applied to a test strip 50. This results ina current signal 52 which is passed stored at 53. During or subsequentto this storage process, the processor 54 evaluates the characteristicsof the current signal and determines t_(peak) and from t_(peak) frommakes determination of t_(meas). Based on the value of t_(meas)appropriate stored current data is retrieved from storage 53, processedby processor 54 to determine a result with is sent to display 57.

FIG. 6 shows an external view of a meter in accordance with theinvention. The meter has a housing 61, and a display 62. The housing 61has a slot 63, into which a test strip is inserted for use. The metermay also have a button 64 for signaling the start of the measurementcycle, or may have an internal mechanism for detecting the insertion ofa test strip or the application of a sample. Such mechanisms are knownin the art, for example from U.S. Pat. Nos. 5,266,179; 5,320,732;5,438,271 and 6,616,819, which are incorporated herein by reference. Inthe meter of the invention, buttons, displays such as LCD displays, rf,infrared or other wireless transmitters, wire connectors such as USB,parallel or serial connections constitute means for receiving input fromand communicating a result to a user, and can be used individually andin various combinations.

Internally, as schematically presented in FIG. 7, the meter of theinvention comprises a potentiostat 71 capable of operating inamperometric mode, a data-storage device 72, such as a flash memory,EEPROMs or battery-backed RAM, and a microprocessor 73 for controllingthe potentiostat 71, processing data, and transmitting acommunication/display to the user interface 74. The microprocessor 73 inthe apparatus of the invention is programmed to determine t_(peak) andthen establish t_(meas) based on the determined t_(peak).

The meter may further comprise means for comparing the determined valueof t_(peak) to a predetermined range, and returning an error messagewhen the determined value falls outside of the range. Exemplary meansfor this purpose are a programmed microprocessor that retrieves therange from memory and performs the comparison.

In one embodiment of the invention, the microprocessor 73 sets the valueof t_(meas) to t_(peak) times a pre-determined factor determined bytesting of electrochemical test strips of the same type as being used inthe meter.

In one embodiment of the invention, the microprocessor 73 samples thecurrent over a range of time determined as a low and a high multiple oft_(peak), evaluates these data points to determine the data point wherethe second derivative of the current versus time plot is closest tozero, and uses this data point to determine the glucose concentration.

EXAMPLE 1

A meter with dynamic determination of t_(meas) using tpeak was used toevaluate finger-stick blood samples from a number diabetic patients,with no selection based on ages, genders, or ethnicity. The samples thusencompassed a good spread of blood physiologies, including different hctlevels and different glucose levels. The test strip employed had facingscreen printed carbon electrodes, and a nominal sample volume of 625nanoliters. Since t_(peak) depends on both mobility of mediator(affected by hct) and by the concentration of glucose (if there ishigher glucose, then more of the mediator must diffuse to the counterelectrode, thereby taking more time), this sampling produced signalswith a good range of different t_(peak) values.

The meter did the measurement, which was to do amperometry until enoughCottrell data was gathered (t_(meas) region), and made glucosedeterminations based on the Cottrell data. The meter also stored thetotal time from sample introduction to LCD display of reading. Thisinformation is summarized in FIG. 4 which is a histogram showing howmany measurements (out of 110) were within each time range. Mostreadings were between 6 to 7 seconds, with an overall average of ˜6.4sec.

EXAMPLE 2

In order to determine the appropriate coefficient to apply in modifyingt_(peak) to determine t_(meas), measurements are taken on matrix ofsamples with a range of hct and glucose concentrations in amperometricmode. An exemplary matrix is

-   -   hct=0, 20, 40, 60, 65%    -   [glu]=˜2 mM up to ˜30 mM

although the important thing is to select ranges that are representativeof typical users. For each glu/hct combination, replicate measurementsare made, and the amperometric data (current vs. time) is compiled.

The data is processed in any of several different ways (as described inFIG. 3A-D to arrive a value of t_(meas). for each data point. Therelationship between t_(peak) and t_(meas) for all the data spanning therange of glucose concentration and hct levels is plotted. The plotteddata points are then fit to a linear model, indicating whether thecorrection is best modeled as an additive correction, a multiplier, orboth. Other models with additional terms may also be employed in fittingthe data.

What is claimed is:
 1. A method for determining an analyte in a samplecomprising the steps of: introducing a sample to be evaluated into anelectrochemical test strip having working and counter electrodes;applying a potential between the electrodes sufficient to generate adiffusion-limited current when analyte is present in the sample;dynamically determining a time, t_(peak), as the time when diffusionlimiting current at the counter electrode is established; sampling thecurrent value at a time, t_(meas), wherein t_(meas) is a multiple oft_(peak), and generating an indication of analyte in the sample based onthe sampled current value at time t_(meas).
 2. The method of claim 1,wherein the multiple is in the range of 1.2 to 1.4.
 3. The method ofclaim 2, wherein the multiple is between 1.25 and 1.35.
 4. The method ofclaim 1, wherein the multiple is in the range of 1.5 to
 5. 5. The methodof claim 4, wherein the multiple is between 3.8 and 4.7.
 6. A method fordetermining an analyte in a sample comprising the steps of: introducinga sample to be evaluated into an electrochemical test strip havingworking and counter electrodes; applying a potential between theelectrodes sufficient to generate a diffusion-limited current whenanalyte is present in the sample; dynamically determining a time,t_(peak), as the time when diffusion limiting current at the counterelectrode is established; sampling the current value at a time,t_(meas), wherein t_(meas) is determined by adding a defined period oftime to t_(peak), and generating an indication of analyte in the samplebased on the sampled current value at time t_(meas).
 7. The method ofclaim 6, wherein the defined period of time is 1.5 to 2 seconds.
 8. Themethod of claim 6, wherein the defined period of time is 6 to 10seconds.